The human genome is billions of DNA ‘letters’ long
Scientists began to map the human genome in 1990. It cost $3 billion and took 13 years. More than 6 billion DNA ‘letters’ make up the genetic blueprint for a human being.
Now the same process costs less than $1,000 and takes 3 days. Affordable new-generation genomic sequencing technologies are transforming our ability to diagnose health conditions and target interventions, especially for rare genetic diseases and cancer.
But genomic sequencing is also prone to errors and technical artefacts. This makes it difficult to analyse the vast amount of data it generates.
Dr Ira Deveson, Head of Genomic Technologies at the Garvan Institute of Medical Research explains:
‘The most common thing you're trying to do in genome sequencing is detect mutations. For someone with cancer you're trying to find a gene somewhere that has a defect. This is a little mistake or “typo” in that gene that is causing the condition.
‘But there are millions of mutations all over the genome and they're challenging to detect.’
Navigating the genome with sequins
To solve this problem, during his PhD, Ira created sequins. Sequins are mirror-image synthetic genomic sequences that represent genes, mutations, or microbes.
Added to a genomic sample, sequins act as internal quality controls. These help researchers check the accuracy of data from each sequenced sample.
Sequins designed and manufactured in Australia are now used by over 200 universities in over 25 countries.
Purpose-built standards for emerging genomic technologies
Funded by a five-year MRFF Investigator Grant, in 2020 Ira began creating sequin standards that are purpose-built for emerging genomic technologies.
The Oxford Nanopore Technologies sequencer was one. For the first time, Nanopore sequencing made real-time, rapid genetic diagnosis possible.
At the height of the COVID pandemic, the new Nanopore sequencer offered the hope of faster COVID variant sequencing. But no-one knew for sure if the results were accurate.
‘In the early stages of 2020 a lot of people started using Nanopore sequencing because it is fast, cheap and portable. They were racing to get it set up. But there were a lot of question marks about whether it was reliable.
‘We resolved that question mark.’
Using sequins and well-characterised natural samples, Ira’s team established a rapid COVID Nanopore sequencing workflow and showed that it was accurate. They published their research which was widely reported in global media.
‘Our paper demonstrated in a rigorous way the advantages and the accuracy of Nanopore sequencing. It was influential in encouraging more wide-spread adoption.’
Public health teams in Victoria, Queensland, and New South Wales, adopted Ira’s workflow. This enabled them to identify the COVID variant of all new cases within 24 hours. Ira’s research group provided training and support for these vital public health initiatives.
Enabling early-career researchers to become next generation leaders
‘I don't think that any of this stuff would have been possible without the support of the MRFF Investigator Grant,’ Ira says. ‘The grant has been hugely beneficial.’
Three months after obtaining his grant, the Garvan Institute of Medical Research hired Ira as a group leader. This meant Ira was able to set up his own lab.
‘I wouldn't have got the role without the grant. Now we have 11 people working in the lab, so it’s a big team. We’ve had a pretty productive couple of years.’
A single DNA test for over 50 genetic diseases cuts diagnosis from decades to days
Recently, Ira used sequins to help develop a single test for over 50 hard to diagnose genetic conditions. This break-through was again reported in global media.
The program for evolution
‘Genomics is fascinating,’ Ira says. ‘It helps us understand and solve many different types of diseases with great prospects to improve human health. It also tells us a huge amount about evolution and how organisms work.
‘Genomes are programs that have been running for more than 3 billion years. They’ve built the hugely complex and amazing organisms that are everywhere on earth.’